The modulatory sites on the GABAA receptor complex, such as for example the benzodiazepine receptor, are the targets for anxiolytic drugs, such as the classical anxiolytic benzodiazepines.
Multiple isoforms of the GABAA receptor exist; each receptor is a pentameric complex comprising subunits drawn from α1-6, β1-3, γ1-3, δ, ε, and θ subunit isoforms. The classical anxiolytic benzodiazepines show no subtype selectivity. It has been suggested that one of the key elements in the disadvantages of the classical benzodiazepanes (such as sedation, dependency, and cognitive impairment) is relates to the α1 subunit of the GABAA receptors. Thus compounds with selectivity for the α2 and/or α3 subunits over the α1 subunit are expected to have an improved side effect profile.
EP 616807 describes benzimidazole compounds for use as benzodiazepine receptor ligands.
WO 96/33194, WO 96/33191 and WO 96/33192 describe benzimidazole compounds having affinity for the GABA receptor complex.
WO 98/34923 describes phenylbenzimidazole derivatives as ligands for the GABA receptor complex.
WO 98/17651 and WO 00/78728 describe benzimidazole compounds for use as e.g. anaesthetics.
However, there is a continued strong need to find compounds with an optimized pharmacological profile. Furthermore, there is a strong need to find effective compounds without unwanted side effects associated with older compounds.